Contrasting effects of intervention with ETA and ETB receptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Erika I. Boesen; Jennifer S. Pollock; David M. Pollock

doi:10.1139/y10-051

Contrasting effects of intervention with ETA and ETB receptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-051 ◽

2010 ◽

Vol 88 (8) ◽

pp. 802-807 ◽

Cited By ~ 12

Author(s):

Erika I. Boesen ◽

Jennifer S. Pollock ◽

David M. Pollock

Keyword(s):

Angiotensin Ii ◽

Creatinine Clearance ◽

Nitrate Concentration ◽

Therapeutic Approaches ◽

Receptor Antagonists ◽

Induced Hypertension ◽

Etb Receptor ◽

Nitrite Nitrate ◽

Plasma Nitrite ◽

Selection Of

Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ETA (ABT-627) or ETB (A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII–HS) in rats. Prior to administration of ABT-627, AngII–HS and AngII–HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 ± 5 and 165 ± 5 mm Hg versus 110 ± 3 mm Hg in normal salt control rats at day 7, P < 0.05). Administering ABT-627 from day 8 of AngII–HS treatment prevented further rises in MAP (168 ± 5 and 191 ± 3 mm Hg at day 13 in AngII–HS plus ABT-627 and AngII–HS, P < 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6- to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII–HS induced hypertension (P < 0.05 for AngII–HS versus AngII–HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P < 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ETA receptor signaling in maintaining AngII–HS hypertension and suggest that including ETB receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.

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Association Analysis for Neuronal Nitric Oxide Synthase Gene Polymorphism with Plasma Nitrite/Nitrate Concentration in Schizophrenia

Journal of Medical Biochemistry ◽

10.2478/jomb-2014-0023 ◽

2014 ◽

Vol 33 (4) ◽

pp. 364-370 ◽

Cited By ~ 2

Author(s):

Vladimir V. Đorđević ◽

Tatjana Jevtović-Stoimenov ◽

Dušan Lazarević ◽

Ivana Stojanović ◽

Ljiljana Trajanović ◽

...

Keyword(s):

Nitric Oxide ◽

Gene Polymorphism ◽

Nitrate Concentration ◽

Polymerase Chain Reaction Analysis ◽

Genotype Distribution ◽

Nucleotide Polymorphisms ◽

Significant Difference ◽

And Gender ◽

Nitrite Nitrate ◽

Plasma Nitrite

Summary Background: Single nucleotide polymorphisms (SNP) of many genes, including the gene for neuronal nitric oxide syn-thase (NOS1), were found significantly associated with schizo-phrenia. According to our previously published results of increased plasma nitric oxide concentration in patients with schizophrenia, we hypothesized that the NOS1 gene polymorphism might be a cause of increased nitric oxide production in patients with schizophrenia and tested the interdependence between plasma nitrite/nitrate concentrations and SNP (a CT transition located in exon 29) of the human NOS1 gene. Methods: Nitrite/nitrate concentration was measured in blood plasma of 38 patients with schizophrenia and of 39 age and gender matched healthy persons by the colorimet-ric test. The NOS1 gene polymorphism was determined by polymerase chain reaction analysis. Results: A significantly higher plasma nitrite/nitrate concentration was found in patients with schizophrenia (97.5±33.3 μmol/L, p<0.001) in comparison with controls (61.4±18.9 μmol/L). No T/T genotype was found in healthy individuals and there was a significant difference in the genotype distribution between patients and controls (χ2=24.54, p=0.0000047). Furthermore, a significant difference in the allele frequencies between patients and controls (χ2=19.00, p<0.000013, OR=4.45, 95% CI=2.12–9.39) was noted. Also, a significant difference in plasma nitrite/nitrate concentration was observed between patients having the C/T genotype (99.97±33.83 μmol/L) and the corresponding control (C/T) subgroup (63.88±10.26 μmol/L, p<0.01). However, there were no significant differences in nitrite/nitrate concentration between the patient subgroups with different genotypes (C/C, C/T, T/T). Conclusions: CT transition located in exon 29 of the human NOS1 gene may be responsible for the increased plasma nitrite/nitrate levels.

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Differential effects of losartan and candesartan on vasoconstrictor responses in the ratThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y06-087 ◽

2007 ◽

Vol 85 (3-4) ◽

pp. 360-371 ◽

Cited By ~ 1

Author(s):

Bobby D. Nossaman ◽

Syed R. Baber ◽

Mohammed M. Nazim ◽

John D. Detrolio ◽

Philip J. Kadowitz

Keyword(s):

Angiotensin Ii ◽

Systemic Arterial Pressure ◽

High Dose ◽

Inhibitory Effects ◽

Receptor Antagonists ◽

Intravenous Injections ◽

Pressor Responses ◽

Tp Receptors ◽

Vascular Beds ◽

Selection Of

Losartan has been reported to have inhibitory effects on thromboxane (TP) receptor-mediated responses. In the present study, the effects of 2 nonpeptide angiotensin II (AT1) receptor antagonists, losartan and candesartan, on responses to angiotensin II, the thromboxane A2 mimic, U46619, and norepinephrine were investigated and compared in the pulmonary and systemic vascular beds of the intact-chest rat. In this study, intravenous injections of angiotensin II, U46619, and norepinephrine produced dose-related increases in pulmonary and systemic arterial pressure. Losartan and candesartan, in the doses studied, decreased or abolished responses to angiotensin II. Losartan, but not candesartan, and only in a higher dose, produced small, but statistically significant, reductions in pressor responses to U46619 and to norepinephrine in the pulmonary and systemic vascular beds. Furthermore, losartan significantly reduced arachidonic acid-induced platelet aggregation, whereas candesartan had no effect. Pressor responses to angiotensin II were not changed by thromboxane and alpha-adrenergic receptor antagonists, or by cyclooxygenase and NO synthase inhibitors. These results show that losartan and candesartan are potent selective AT1 receptor antagonists in the pulmonary and systemic vascular beds and that losartan can attenuate thromboxane and alpha-adrenergic responses when administered at a high dose, whereas candesartan in the highest dose studied had no effect on responses to U46619 or to norepinephrine. The present data show that the effects of losartan and candesartan on vasoconstrictor responses are different and that pulmonary and systemic pressor responses to angiotensin II are not modulated or mediated by the release of cyclooxygenase products, activation of TP receptors, or the release of NO in the anesthetized rat.

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